# US 11,299,473 B2 · Benzimidazole and indole compounds and uses thereof

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- Number: US 11,299,473 B2
- Document ID: US11299473B2
- Status: Granted
- Kind: B2
- Application number: 16/382,482
- Filed: 2019-04-12
- Published: 2019-10-17
- Granted: 2022-04-12
- Earliest claimed: 2018-04-13
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Joshua Hummel; Minh Nguyen; Alexander Sokolsky; Oleg Vechorkin; Qinda Ye; Wenqing Yao
- Web page: https://patentgrep.com/patent/US11299473B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 35/00: Antineoplastic agents
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

## Claims

### Claim 1

A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, SRa, C(O)Rb, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(=NRe)Rb, C(═NORa)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, S(O)2NRcRd and BRhRi; wherein said C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
X is N or CRZ, and Y is NRY; or
X is NRX or CHRZ, and Y is N;
dashed bond represents a single or double bond, wherein one dashed bond is a single bond and the other dashed bond is a double bond;
R2 is selected from H, D, Cy2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NORa2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2 and BRh2Ri2; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
R3 and R4 are each independently selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and BRh3Ri3; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
R5 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5 and BRh5Ri5; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
R6 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6 and BRh6Ri6; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
A is N;
CyB is selected from C5-10 cycloalkyl, C6-10 aryl and 5-6 membered heteroaryl; wherein the 5-6 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2 or 3 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-6 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C5-10 cycloalkyl, C6-10 aryl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R7;
RX and RY are each independently selected from H, D, CyN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, C(═NRc4)Rb4, C(═NORa4)Rb4, (═NRc4)NRc4Rd4, NRc4C (═NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4 and S(O)2NRc4Rd4, wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
RZ is selected from H, D, CyZ, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa10, SRa10, C(O)Rb10, C(O)NRc10Rd10, C(O)ORa10, OC(O)Rb10, OC(O)NRc10Rd10, CN, NO2, OR NRc10Rd10, NRc10C(O)Rb10, NRc10C(O)ORa10, NRc10C(O)NRc10Rd10, C(═NRe10)Rb10, C(═NORa10)Rb10, C(═NRe10)NRc10Rd10, NRc10C(═NRe10)NRc10Rd10, NRc10S(O)Rb10, NRc10S(O)2Rb10, NRc10S(O)2NRc10Rd10, S(O)Rb10, S(O)NRc10Rd10, S(O)2Rb10, S(P)2NRc10Rd10 and BRh10Ri10; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each R7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7C(O)NRc7Rd7, C(═NRe7)Rb7, C(═NORa7)Rb7, (═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc7Rd7, NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7 and BRh7Ri7; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R8;
each R8 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa8, SRa8, C(O)Rb8, C(O)NRc8Rd8, C(O)ORa8, NRc8Rd8, NRc8C(O)Rb8, NRc8C(O)ORa8, NRc8 S(O)Rb8, NRc8 S(O)2Rb8, NRc8S(O)2NRc8Rd8, S(O)Rb8, S(O)NRc8Rd8, S(O)2Rb8, S(O)2NRc8Rd9 and BRh8Ri8; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R9;
each R9 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa9, SRa9, C(O)Rb9, C(O)NRc9Rd9, C(O)ORa9, NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9 NRc9S(O)Rb9, NRc9S(O)2Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, and S(O)2NRc9Rd9; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
Cy1 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(═NRe1)Rb1, C(═NORa1)Rb1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1 and BRh1Ri1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1_3 alkylene, 4-10 membered heterocycloalkyl-C1_3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa11, SRa11, (O)Rb11, C(O)NRc11Rd11, C(O)Ra11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11S(O)Rb11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, S(O)2NRc11Rd11 and BRh11Ri11; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
each R12 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12S(O)Rb12, NRc12S(O)2Rb12, NRc12S(O)2NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, S(O)2NRc12Rd12 and BRh12R112; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
Cy2 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa13, SRa13, C(O)Rb13, C(O)NRc13Rd13, C(O)ORa13, OC(O)Rb13, OC(O)NRc13Rd13, NRc13Rd13, NRc13C(O)Rb13, NRc13C(O)ORa13, NRc13C(O)NRc13Rd13, C(═NRe13)Rb13, C(═NORa13)Rb13, C(═NRe13)NRc13Rd13, NRc13C(═NRe13)NRc13Rd13, NRc13S(O)Rb13, NRc13S(O)2Rb13, NRc13S(O)2NRc13Rd13, S(O)Rb13, S(O)NRc13Rd13, S(O)2Rb13, S(O)2NRc13Rd13 and BRh13Ri13; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-11) aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-Ci-3 alkylene, C6-10 aryl-Ci-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R14;
each R14 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa14, SRa14, C(O)Rb14, C(O)NRc14Rd14, C(O)ORa14, NRc14Rd14, NRc14C(O)Rb14, NRc14C(O)ORa14, NRc14S(O)Rb14, NRc14S(O)2Rb14, NRc14S(O)2NRc14Rd14, S(O)Rb14, S(O)NRc14Rd14, S(O)2Rb14, S(O)2NRc14Rd14 and BRh14Ri14; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R15;
each R15 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa15, SRa15, C(O)Rb15, C(O)NRc15Rd15, C(O)ORa15, NRc15Rd15, NRc15C(O)Rb15, NRc15C(O)ORa15, NRc15S(O)Rb15, NRc15S(O)2Rb15, NRc15S(O)2NRc15Rd15, S(O)Rb15, S(O)NRc15Rd15, S(O)2Rb15, and S(O)2NRc15Rd15; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
CyZ and CyN are each independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Ra, Rc, and Rd is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
or any Rc and Rd attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each Rb is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
each Re is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl;
each Rh and Ri is independently selected from OH and C1-6 alkoxy;
or any Rh and Ri attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra1, Rc1 and Rd1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
or any Rc1 and Rd1 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
each Rb1 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each Re1 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl;
each Rh1 and Ri1 is independently selected from OH and C1-6 alkoxy;
or any Rh1 and Ri1 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each Rc2 and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Rb2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each Re2 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl;
each Rh2 and Ri2 is independently selected from OH and C1-6 alkoxy;
or any Rh2 and Ri2 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb3 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh3 and Ri3 is independently selected from OH and C1-6 alkoxy;
or any Rh3 and Ri3 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra4, Rc4 and Rd4 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
or any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Rb4 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each Re4 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl;
each Ra5 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rc5 and Rd5 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb5 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh5 and Ri5 is independently selected from OH and C1-6 alkoxy;
or any Rh5 and Ri5 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb6 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh6 and Ri6 is independently selected from OH and C1-6 alkoxy;
or any Rh6 and Ri6 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra7, Rc7 and Rd7 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R8;
or any Rc7 and Rd7 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R8;
each Rb7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R8;
each Re7 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl;
each Rh7 and Ri7 is independently selected from OH and C1-6 alkoxy;
or any Rh7 and Ri7 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra8, Rc8 and Rd8 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R9;
or any Rc8 and Rd8 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R9;
each Rb8 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R9;
each Rh8 and Ri8 is independently selected from OH and C1-6 alkoxy;
or any Rh8 and Ri8 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra9, Rc9 and Rd9 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb9 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Ra10, Rc10, and Rd10 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
or any Rc10 and Rd10 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Rb10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each Re10 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl;
each Rh10 and Ri10 is independently selected from OH and C1-6 alkoxy;
or any Rh10 and Ri10 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra11, Rc11 and Rd11 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
or any Rc11 and Rd11 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R12;
each Rb11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl;
wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
each Rh11 and Ri11 is independently selected from OH and C1-6 alkoxy;
or any Rh11 and Ri11 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra12, Rc12 and Rd12 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb12 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh12 and Ri12 is independently selected from OH and C1-6 alkoxy;
or any Rh12 and Ri12 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra13, Rc13 and Rd13 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R14;
or any Rc13 and Rd13 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R14;
each Rb13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R14;
each Re13 is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, amino sulfonyl, C1-6 alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl;
each Rh13 and Ri13 is independently selected from OH and C1-6 alkoxy;
or any Rh13 and Ri13 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra14, Rc14 and Rd14 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R15;
or any Rc14 and Rd14 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R15;
each Rb14 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R15;
each Rh14 and Ri14 is independently selected from OH and C1-6 alkoxy;
or any Rh14 and Ri14 attached to the same B atom are C2-3 dialkoxy and together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from C1-6 alkyl;
each Ra15, Rc15 and Rd15 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rb15 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; and
each Rg is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-2 alkylene, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-3 alkoxy-C1-3 alkoxy, HO—C1-3 alkoxy, HO—C1-3 alkyl, cyano-C1-3 alkyl, H2N—C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyB is selected from C5-10 cycloalkyl and C6-10 aryl; wherein the C5-10 cycloalkyl and C6-10 aryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R7.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyB is C6-10 aryl optionally substituted with 1, 2, or 3 substituents independently selected from R7.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyB is phenyl optionally substituted with 1, 2, or 3 substituents independently selected from R7.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, NRc7Rd7 NRc7C(O)Rb7, and NRc7C(O)ORa7.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R7 is independently selected from C1-6 alkyl, halo, and ORa7.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyB is phenyl substituted with 1, 2 or 3 substituents selected from fluoro, methoxy, and methyl.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, SRa, C(O)Rb, C(O)ORa, NRcRd, and NRcC(O)Rb; wherein said C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from Cy1 and NRcRd.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is Cy1.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy1 is selected from 4-10 membered heterocycloalkyl and C6-10 aryl; wherein the 4-10 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and C6-10 aryl are each optionally substituted with 1, 2 or 3 substituents independently selected from R10.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy1 is 4-10 membered heterocycloalkyl; wherein the 4-10 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy1 is C6-10 aryl optionally substituted with 1 or 2 substituents independently selected from R10.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa1, SRa1, NRc1Rd1, NRc1C(O)Rb1, and NRc1C(O)ORa1; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2 or 3 substituents independently selected from R11.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R10 is independently selected from C1-6 alkyl and NRc1Rd1; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa11, and NRc11Rd11.

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R11 is independently selected from ORa11 and NRc11Rd11.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is NRcRd.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is 4-amino-2-(hydroxymethyl)pyrrolidin-1-yl; methyl(piperidin-3-yl)amino; 3-(aminomethyl)morpholino; 2-(hydroxymethyl)piperazin-1-yl; 2,5-diazabicyclo[2.2.1]heptan-2-yl; 2-oxa-5-azabicyclo[2.2.1]heptan-5-yl; 2-(aminomethyl)pyrrolidin-1-yl; 3-aminopyrrolidin-1-yl; 2-aminophenyl; or 2-methylpiperazin-1-yl.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is N or CRZ, and Y is NRY.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is N and Y is NRY.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is CRZ and Y is NRY.

### Claim 23 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is selected from H, D, CyN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and halo; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13.

### Claim 24 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is selected from H, D, CyN, and C1-6 alkyl; wherein said C1-6 alkyl is each optionally substituted with 1, 2, or 3 substituents independently selected from R13.

### Claim 25 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is CyN.

### Claim 26 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein CyN is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2 or 3 substituents independently selected from R13.

### Claim 27 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is C1-6 alkyl optionally substituted with 1 or 2 substituents independently selected from R13.

### Claim 28 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is H, D, methyl, cyclopropyl, 2-methoxyethyl, 1-methoxypropan-2-yl, 2-methoxy-2-methylpropyl, tetrahydrofuranyl, pyridin-4-ylmethyl, (1-methyl-1H-pyrazol-4-yl)methyl, tetrahydro-2H-pyran-2-yl)methyl, 2-methylthiazol-5-yl)methyl, 2-morpholinoethyl, 2-methoxypyridin-4-yl, 2-fluoro-4-methoxyphenyl, 1-methyl-1H-pyrazol-5-yl, or 2-cyano-3-fluorophenyl.

### Claim 29 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RY is H.

### Claim 30 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein RZ is H.

### Claim 31 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, D, Cy2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(O)Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R13.

### Claim 32 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, D, Cy2, and C1-6 alkyl; wherein said C1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from R13.

### Claim 33 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is Cy2.

### Claim 34 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy2 is selected from 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R13.

### Claim 35 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is C1-6 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from R13.

### Claim 36 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is H, 3-fluoropyridin-2-yl, 3-methoxypyridin-2-yl, 2-cyanophenyl, 3,5-difluoropyridin-4-yl, 3-fluoropyridin-4-yl, methyl, isopropyl, 1-methyl-1H-pyrazol-5-yl, tetrahydro-2H-pyran-4-yl, methoxymethyl, or 2-methoxyethyl.

### Claim 37 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa13, SRa13, C(O)b13, C(O)NRc13Rd13, C(O)ORa13, NRc13Rd13, and NRc13C(O)Rb13; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2 or 3 substituents independently selected from RM.

### Claim 38 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, and ORa13; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2 or 3 substituents independently selected from RM.

### Claim 39 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R13 is independently selected from C1-6 alkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, and ORa13; wherein said C1-6 alkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2 or 3 substituents independently selected from R14.

### Claim 40 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are each H.

### Claim 41 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is H.

### Claim 42 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R6 is H.

### Claim 43 (depends on 1)

The compound of claim 1 having Formula II:
or a pharmaceutically acceptable salt thereof.

### Claim 44 (depends on 1)

The compound of claim 1 having Formula IIIa:
or a pharmaceutically acceptable salt thereof.

### Claim 45 (depends on 1)

The compound of claim 1 having Formula IIIb:
or a pharmaceutically acceptable salt thereof.

### Claim 46 (depends on 1)

The compound of claim 1 having Formula Vb or Formula Vd:
or a pharmaceutically acceptable salt thereof, wherein m is 1, 2, 3, or 4.

### Claim 47 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-fluoropyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-fluoropyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-methoxypyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(2-cyanophenyl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(2-cyanophenyl)-1-cyclopropyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
(R)-2-(2,6-Difluorophenyl)-N-(2-(3,5-difluoropyridin-4-yl)-1-methyl-4-(methyl(piperidin-3-yl)amino)-1H-benzo[d]imidazol-5-yl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-fluoropyridin-4-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(3-(Aminomethyl)morpholino)-2-(3-fluoropyridin-4-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(R)-2-(2,6-Difluorophenyl)-N-(2-(3-fluoropyridin-4-yl)-4-(2-(hydroxymethyl)piperazin-1-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)pyrimidine-4-carboxamide;
N-(4-((1 S,4 S)-2,5-Diazabicyclo [2.2.1]heptan-2-yl)-2-(3-fluoropyridin-4-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1 S,4 S)-2-Oxa-5-azabicyclo [2.2.1]heptan-5-yl)-2-(3-fluoropyridin-4-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(R)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(R)-2-(2-Fluoro-6-methoxyphenyl)-N-(4-(2-(hydroxymethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)pyrimidine-4-carboxamide;
N-(4-((2 S,4R)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1R,4R)-2,5-Diazabicyclo [2.2.1]heptan-2-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1 S,4 S)-2,5-Diazabicyclo [2.2.1]heptan-2-yl)-2-isopropyl-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-2-(3-fluoropyridin-4-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-methyl-2-(1-methyl-1H-pyrazol-5-yl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-methyl-2-(tetrahydro-2H-pyran-4-yl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-(2-methoxyethyl)-2-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((S)-2-(Aminomethyl)pyrrolidin-1-yl)-1-((R)-1-methoxypropan-2-yl)-2-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-(2-methoxy-2-methylpropyl)-2-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((S)-2-(Aminomethyl)pyrrolidin-1-yl)-2-methyl-1-((S)-tetrahydrofuran-3-yl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-2-(methoxymethyl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-2-(2-methoxyethyl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((S)-2-(Aminomethyl)pyrrolidin-1-yl)-1-((R)-tetrahydrofuran-3-yl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(3-Aminopyrrolidin-1-yl)-2-methyl-1-(pyridin-4-ylmethyl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(3-Aminopyrrolidin-1-yl)-2-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-(2-Aminophenyl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide;
(S)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1,2-dimethyl-1H-benzo[d]imidazol-5-yl)-2-(2-fluoro-6-methylphenyl)pyrimidine-4-carboxamide;
(R)—N-(4-(2-(Aminomethyl)pyrrolidin-1-yl)-1-methyl-1-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4 S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-1-methyl-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
(R)-2-(2-Fluoro-6-methoxyphenyl)-N-(1-methyl-4-(2-methylpiperazin-1-yl)-1H-indol-5-yl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-methyl-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-(pyridin-4-ylmethyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-((tetrahydro-2H-pyran-2-yl)methyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-((2-methylthiazol-5-yl)methyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-(2-morpholinoethyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-2-yl)-1-(2-methoxypyridin-4-yl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4 S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-1-(2-fluoro-4-methoxyphenyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
N-(4-((2 S,4 S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-1-(1-methyl-1H-pyrazol-5-yl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide; and
N-(4-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)-1-(2-cyano-3-fluorophenyl)-1H-indol-5-yl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide;
or a pharmaceutically acceptable salt thereof.

### Claim 48 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, SRa, C(O)Rb, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd; wherein said C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
X is N or CRZ, and Y is NRY;
dashed bond represents a single or double bond, wherein one dashed bond is a single bond and the other dashed bond is a double bond;
R2 is selected from H, D, Cy2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
R3 and R4 are each independently selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
R5 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
R6 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
A is N;
CyB is selected from C6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R7;
RX and RY are each independently selected from H, D, CyN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4 and S(O)2NRc4Rd4; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
RZ is selected from H, D, CyZ, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and halo; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
each R7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, and NRc7C(O)NRc7Rd7;
Cy1 is selected from 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, and NRc1C(O)ORa1; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)Ra11, NRc11Rd11, NRc11C(O)Rb11, and NRc11C(O)ORa11;
Cy2 is selected from 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa13, SRa13, C(O)Rb13, C(O)NRc13Rd13, C(O)ORa13, OC(O)Rb13, OC(O)NRc13Rd13, NRc13Rd13, NRc13C(O)Rb13, NRc13C(O)ORa13 and NRc13C(O)NRc13Rd13; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R14;
each R14 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, and CN;
CyZ and CyN are each independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Ra, Rc, and Rd is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and 4-10 membered heterocycloalkyl;
each Rb is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra1, Rc1 and Rd1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Rb1 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Rc2 and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Rb2 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra4, Rc4 and Rd4 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Rb4 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra7, Rc7 and Rd7 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Rb7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra11, Rc11 and Rd11 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Rb11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
each Ra13, Rc13 and Rd13 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; and
each Rb13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

### Claim 49 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, and NRcRd; wherein said C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R10;
X is N or CRZ, and Y is NRY;
dashed bond represents a single or double bond, wherein one dashed bond is a single bond and the other dashed bond is a double bond;
R2 is selected from H, D, Cy2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, and NRc2C(O)Rb2, wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
R3 and R4 are each independently selected from H, D, and C1-6 alkyl;
R5 is selected from H, D, and C1-6 alkyl;
R6 is selected from H, D, and C1-6 alkyl;
A is N;
CyB is selected from C6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R7;
RX and RY are each independently selected from H, D, CyN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and halo; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R13;
RZ is selected from H, D, and C1-6 alkyl;
each R7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, and C(O)ORa7;
Cy1 is selected from 4-10 membered heterocycloalkyl and C6-10 aryl; wherein the 4-10 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and C6-10 aryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, NRc1Rd1, NRc1C(O)Rb1, and NRc1C(O)ORa1; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, D, CN, ORa11, NRc11Rd11, NRc11C(O)Rb11, and NRc11C(O)ORa11;
Cy2 is selected from 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each R13 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, D, CN, NO2, ORa13, SRa13, C(O)Rb13, C(O)NRc13Rd13, C(O)ORa13, NRc13Rd13, and NRc13C(O)Rb13; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from RM;
each R14 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and D;
CyZ and CyN are each independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Rc and Rd is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and 4-10 membered heterocycloalkyl;
each Ra1, Rc1 and Rd1 is independently selected from H and C1-6 alkyl;
each Rb1 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Ra2 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Rc2 and Rd2 is independently selected from H and C1-6 alkyl;
each Rb2 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Ra7, Rc7 and Rd7 is independently selected from H and C1-6 alkyl;
each Rb7 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Ra11, Rc11 and Rd11 is independently selected from H and C1-6 alkyl;
each Rb11 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
each Ra13, Rc13 and Rd13 is independently selected from H and C1-6 alkyl; and
each Rb13 is independently selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl.

### Claim 50 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from Cy1 and NRcRd;
X is N or CRZ, and Y is NRY;
dashed bond represents a single or double bond, wherein one dashed bond is a single bond and the other dashed bond is a double bond;
R2 is selected from H, Cy2, and C1-6 alkyl; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R13;
R3 and R4 are H;
R5 is H;
R6 is H;
A is N;
CyB is selected from phenyl optionally substituted with 1 or 2 substituents independently selected from R7;
RX and RY are each independently selected from H, CyN, and C1-6 alkyl; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R13;
RZ is H;
each R7 is independently selected from C1-6 alkyl, halo, and ORa7;
Cy1 is selected from 4-10 membered heterocycloalkyl and C6-10 aryl; wherein the 4-10 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl and C6-10 aryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
each R10 is independently selected from C1-6 alkyl and NRc1Rd1; wherein said C1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
each R11 is independently selected from ORa11 and NRc11Rd11;
Cy2 is selected from 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each R13 is independently selected from C1-6 alkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halo, CN, and ORa13; wherein said C1-6 alkyl and 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R14;
R14 is C1-6 alkyl;
CyN are each independently selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
each Rc and Rd is independently selected from H, C1-6 alkyl, and 4-10 membered heterocycloalkyl;
Rc1 and Rd1 are H;
Ra7 is C1-6 alkyl;
Ra11, Rc11 and Rd11 are H; and
each Ra13, Rc13 and Rd13 is independently selected from H and C1-6 alkyl.

### Claim 51 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

### Claim 52 (depends on 1)

A method of inhibiting HPK1 activity, said method comprising contacting a compound of claim 1, or a pharmaceutically acceptable salt thereof with HPK1.

### Claim 53 (depends on 52)

The method of claim 52, wherein the contacting comprises administering the compound to a patient.

### Claim 54 (depends on 1)

A method of treating a disease or disorder associated with inhibition of HPK1 interaction, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 55 (depends on 1)

A method for treating a cancer in a patient, said method comprising: administering to the patient a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 56 (depends on 55)

The method of claim 55, wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.